Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial

May 5, 2026 updated by: NRG Oncology

A Phase III Randomized Clinical Trial of Proton Craniospinal Irradiation Versus Involved-Field Radiotherapy for Patients With Breast Cancer or Non-Small Cell Lung Cancer Leptomeningeal Metastasis (Radiate-LM)

This phase III trial compares proton craniospinal irradiation (pCSI) to involved-field radiation therapy (IFRT) for the treatment of breast or non-small cell lung cancer that has spread from where it first started to the cerebrospinal fluid filled space that surrounds the brain and spinal cord (leptomeningeal metastasis). Patients with leptomeningeal metastasis (LM) may develop multiple areas of nervous system (neurologic) impairment that can be life-threatening. Radiation therapy (RT) effectively relieves local symptoms due to LM. RT uses high energy radiography (x-rays), particles, or radioactive seeds to kill cancer cells and shrink tumors. IFRT is commonly used to treat symptoms of LM. IFRT is radiation treatment that uses x-rays to treat specific areas of LM and to relieve and/or prevent symptoms. pCSI uses protons that can be directed with more accuracy than x-rays which allows treatment of the entire central nervous system space containing the cerebrospinal fluid (CSF), brain, and spinal cord. The pCSI treatment could delay the worsening of LM. Giving pCSI may be better than IFRT in treating LM in patients with breast or non-small cell lung cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare overall survival (OS) between proton craniospinal irradiation (pCSI) and involved-field radiotherapy (IFRT) in patients with breast cancer or non-small cell lung cancer (NSCLC) leptomeningeal metastasis.

SECONDARY OBJECTIVES:

I. To compare central nervous system progression-free survival (CNS PFS) between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.

II. To compare time to CNS progression between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.

III. To compare CNS PFS between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis, as evaluated by central review of imaging.

IV. To compare the rate of radiation-induced central nervous system necrosis between pCSI versus (vs.) IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.

V. To characterize treatment-related adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

VI. To compare patient-reported outcomes (symptoms severity subscale per MD Anderson Symptom Inventory for Brain Tumors [MDASI-BT] and MD Anderson Symptom Inventory for Spine Tumors [MDASI-SP]) in patients with breast cancer or non-small cell lung cancer leptomeningeal metastasis.

EXPLORATORY OBJECTIVE:

I. To compare patient-reported outcomes (symptoms interference, brain tumor-specific, spine tumor-specific subscales per MDASI-BT and MDASI-SP) in patients with breast cancer or non-small cell lung cancer leptomeningeal metastasis.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo involved-field radiation therapy delivered to specific areas of LM that are causing and/or may cause symptoms 5 days a week for a total of 10 days of treatment in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT during screening and magnetic resonance imaging (MRI) as well as possible lumbar puncture (LP) throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study.

ARM 2: Patients undergo pCSI radiation therapy delivered to the entire space containing the CSF, brain, and spinal cord 5 days a week for a total of 10 days of treatment in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT during screening and MRI as well as possible LP throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study.

After completion of study treatment, patients are followed every 3 months for 12 months, and then every 6 months for up to 3 years from end of RT.

Study Type

Interventional

Enrollment (Estimated)

115

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital in Arizona
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Eric Lehrer
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 501-686-8274
        • Principal Investigator:
          • Fen Xia
    • California
      • Encinitas, California, United States, 92024
        • Recruiting
        • UC San Diego Health System - Encinitas
        • Principal Investigator:
          • Jona A. Hattangadi-Gluth
        • Contact:
          • Site Public Contact
          • Phone Number: 760-536-7700
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Principal Investigator:
          • Jona A. Hattangadi-Gluth
        • Contact:
      • San Diego, California, United States, 92103
        • Recruiting
        • UC San Diego Medical Center - Hillcrest
        • Principal Investigator:
          • Jona A. Hattangadi-Gluth
        • Contact:
      • San Diego, California, United States, 92121
        • Recruiting
        • California Protons Cancer Therapy Center
        • Principal Investigator:
          • Jona A. Hattangadi-Gluth
        • Contact:
          • Site Public Contact
          • Phone Number: 858-299-5982
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20016
        • Recruiting
        • Sibley Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Carmen Kut
    • Florida
      • Aventura, Florida, United States, 33180
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Aventura
        • Contact:
          • Site Public Contact
          • Phone Number: 954-461-2180
        • Principal Investigator:
          • Morgan Freret
      • Coral Gables, Florida, United States, 33146
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Morgan Freret
      • Deerfield Beach, Florida, United States, 33442
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Morgan Freret
      • Doral, Florida, United States, 33166
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Doral
        • Contact:
        • Principal Investigator:
          • Morgan Freret
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Morgan Freret
      • Miami, Florida, United States, 33176
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Kendall
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Morgan Freret
      • Miami, Florida, United States, 33176
        • Recruiting
        • Miami Cancer Institute
        • Principal Investigator:
          • Matthew D. Hall
        • Contact:
          • Site Public Contact
          • Phone Number: 786-596-2000
      • Plantation, Florida, United States, 33324
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Plantation
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Morgan Freret
    • Illinois
      • Alton, Illinois, United States, 62002
        • Recruiting
        • Alton Memorial Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 618-463-7323
        • Principal Investigator:
          • Nikhil Rammohan
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
      • Shiloh, Illinois, United States, 62269
        • Recruiting
        • Memorial Hospital East
        • Contact:
        • Principal Investigator:
          • Nikhil Rammohan
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Contact:
        • Principal Investigator:
          • Vinai Gondi
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
        • Principal Investigator:
          • Danielle Cunningham
      • Overland Park, Kansas, United States, 66210
        • Recruiting
        • University of Kansas Cancer Center-Overland Park
        • Contact:
        • Principal Investigator:
          • Danielle Cunningham
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Carmen Kut
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University/Karmanos Cancer Institute
        • Principal Investigator:
          • Brian K. Yeh
        • Contact:
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Weisberg Cancer Treatment Center
        • Principal Investigator:
          • Brian K. Yeh
        • Contact:
      • Flint, Michigan, United States, 48532
        • Recruiting
        • McLaren Cancer Institute-Flint
        • Principal Investigator:
          • Brian K. Yeh
        • Contact:
      • Lansing, Michigan, United States, 48910
        • Recruiting
        • Karmanos Cancer Institute at McLaren Greater Lansing
        • Principal Investigator:
          • Brian K. Yeh
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Eric Lehrer
    • Missouri
      • City of Saint Peters, Missouri, United States, 63376
        • Recruiting
        • Siteman Cancer Center at Saint Peters Hospital
        • Contact:
        • Principal Investigator:
          • Nikhil Rammohan
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Contact:
        • Principal Investigator:
          • Nikhil Rammohan
      • Kansas City, Missouri, United States, 64154
        • Recruiting
        • University of Kansas Cancer Center - North
        • Contact:
        • Principal Investigator:
          • Danielle Cunningham
      • Lee's Summit, Missouri, United States, 64064
        • Recruiting
        • University of Kansas Cancer Center - Lee's Summit
        • Contact:
        • Principal Investigator:
          • Danielle Cunningham
      • Springfield, Missouri, United States, 65804
        • Recruiting
        • Mercy Hospital Springfield
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
          • Site Public Contact
          • Phone Number: 417-269-4520
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Nikhil Rammohan
      • St Louis, Missouri, United States, 63128
        • Recruiting
        • Mercy Hospital South
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
      • St Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Contact:
        • Principal Investigator:
          • Nikhil Rammohan
      • St Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Contact:
        • Principal Investigator:
          • Nikhil Rammohan
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
    • New York
      • Brooklyn, New York, United States, 11220
        • Recruiting
        • NYU Langone Hospital - Brooklyn
        • Contact:
        • Principal Investigator:
          • Jonathan T. Yang
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
      • East White Plains, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
      • Mineola, New York, United States, 11501
        • Recruiting
        • NYU Langone Hospital - Long Island
        • Contact:
        • Principal Investigator:
          • Jonathan T. Yang
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
      • New York, New York, United States, 10016
        • Recruiting
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
        • Contact:
        • Principal Investigator:
          • Jonathan T. Yang
      • New York, New York, United States, 10035
        • Recruiting
        • New York Proton Center
        • Contact:
        • Principal Investigator:
          • Arpit M. Chhabra
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center-Einstein Campus
        • Principal Investigator:
          • Jana L. Fox
        • Contact:
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center - Moses Campus
        • Principal Investigator:
          • Jana L. Fox
        • Contact:
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Yao Yu
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Joshua D. Palmer
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Jerry J. Jaboin
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Rachna Malani
    • Virginia
      • Alexandria, Virginia, United States, 22304
        • Recruiting
        • Inova Alexandria Hospital
        • Contact:
        • Principal Investigator:
          • Avani D. Rao
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Principal Investigator:
          • Avani D. Rao
        • Contact:
      • Fairfax, Virginia, United States, 22033
        • Recruiting
        • Inova Fair Oaks Hospital
        • Principal Investigator:
          • Avani D. Rao
        • Contact:
      • Leesburg, Virginia, United States, 20176
        • Recruiting
        • Inova Loudoun Hospital
        • Principal Investigator:
          • Avani D. Rao
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION
  • Patients with pathologically (histologically or cytologically) proven diagnosis of breast cancer or NSCLC

  • Patients must have newly diagnosed leptomeningeal metastasis established through at least one of the following:

    • Positive CSF cytology for malignancy

      • CSF cytology with suspicious cells is considered positive; CSF cytology with atypical cells is considered equivocal and not positive

    • Patients with an equivocal or negative CSF cytology result, or not suitable for CSF sampling, radiographic diagnosis of leptomeningeal metastasis with linear and/or nodular disease and documentation of typical clinical signs (European Association of Neuro-Oncology [EANO]-European Society for Medical Oncology [ESMO] Diagnostic Criteria Type IIA-IIC) is required

      • Patients with typical clinical signs of leptomeningeal metastasis may have one or more of the following symptoms and signs: headache, nausea, vomiting, mental status change, gait difficulty, cranial nerve palsy, diplopia, visual change, hearing loss, radicular weakness, radicular sensory change, urinary retention, saddle anesthesia, constipation, neck pain, and back pain
    • For patients with prior history of immunotherapy or current immunotherapy, CSF sampling rather than just MRI enhancement is strongly recommended to exclude immune-related aseptic meningitis
  • Patients must be candidates for radiation therapy for the treatment of leptomeningeal metastasis
  • Age ≥ 18
  • PRIOR TO STEP 2 REGISTRATION
  • Note: Step 2 registration must occur no later than 30 calendar days after step 1 registration
  • Financial clearance for proton therapy treatment
  • Patients must have systemic disease evaluation through standard of care imaging for example CT chest/abdomen/pelvis or body PET/CT
  • Karnofsky performance status ≥ 60

  • Not pregnant and not nursing

    • Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
  • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 8.0 g/dl is acceptable)
  • Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (Note: the use of granulocyte-colony stimulating factor or other intervention to achieve ANC ≥ 1,000/mm^3 is acceptable)
  • Platelets ≥ 100,000/mm^3 (Note: the use of transfusion or other intervention to achieve platelets ≥ 100,000/mm^3 is acceptable)
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (patients with known Gilbert disease without other clinically significant liver abnormalities are not excluded)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × ULN
  • No prior radiation therapy to the spinal cord with equivalent dose in 2 gray (Gy) fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using alpha/beta ratio of 3
  • No prior treatment for leptomeningeal metastasis (note: prior CNS treatment for other non-leptomeningeal disease is allowed)
  • No history of unstable angina requiring hospitalization in the last 3 months
  • No history of myocardial infarction within the last 3 months
  • New York Heart Association Functional Classification II or better (New York Heart Association [NYHA] Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
  • No active infection currently requiring intravenous (IV) antibiotic management
  • No active chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy
  • No CTCAE v5.0 ≥ grade 2 encephalopathy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1 (IFRT)
Patients undergo involved-field radiation therapy delivered to specific areas of LM that are causing and/or may cause symptoms 5 days a week for a total of 10 days of treatment in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT during screening and MRI as well as LP throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Lumbar Puncture
Undergo LP
Other Names:
  • LP
  • Spinal Tap
Radiation: Involved-Field Radiation Therapy
Undergo IFRT
Other Names:
  • IFRT
  • Involved field radiotherapy
Procedure: Biospecimen Collection
Undergo blood and CSF sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Experimental: Arm 2 (pCSI)
Patients undergo pCSI radiation therapy delivered to the entire space containing the CSF, brain, and spinal cord 5 days a week for a total of 10 days of treatment in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT during screening and MRI as well as possible LP throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Lumbar Puncture
Undergo LP
Other Names:
  • LP
  • Spinal Tap
Procedure: Biospecimen Collection
Undergo blood and CSF sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Radiation: Proton Beam Craniospinal Irradiation
Undergo pCSI
Other Names:
  • Craniospinal Proton Beam Radiation Therapy
  • p-CSI
  • Proton Craniospinal Irradiation
  • Proton Craniospinal Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: From randomization until death due to any cause, assessed up to 3 years
Will be event-driven and will be conducted when a total of 88 OS events (from both treatment arms) have been observed. The final analysis (if the trial does not stop early at an interim) is expected to occur roughly 45 months after study activation (including the initial 6-months ramp-up). All analyses (interim or final) will be done on a modified intent-to-treat (ITT) basis such that all randomized patients who have follow-up information will be included in the arm to which they are randomized regardless of what treatment the patients receive. Treatment comparisons will be based on the log-rank test. At the final analysis, if the test has an associated 1-sided p-value of 0.024 or less in favor of proton craniospinal irradiation (pCSI) (equivalently, Z > 1.98), then the trial will conclude that the pCSI arm results in improved survival over the involved field radiotherapy (IFRT) arm.
From randomization until death due to any cause, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central nervous system (CNS) progression-free survival (PFS)
Time Frame: Randomization until CNS progression or death, whichever occurs first, assessed up to 3 years
Will be based on modified ITT, including all randomized patients who have follow-up information. The analysis will be performed according to the treatment arm to which patients were randomized. Analysis for CNS-PFS will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a log-rank test. Statistical power will depend on the total CNS-PFS events accumulated at trial end. Additional analyses may consist of estimating the treatment hazard ratio via the Cox proportional hazards model accounting for prognostic covariates including randomization stratification factors evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying, and evaluating for potential treatment by prognostic covariate interactions.
Randomization until CNS progression or death, whichever occurs first, assessed up to 3 years
Time to CNS progression
Time Frame: Randomization until CNS progression, assessed up to 3 years
Analysis for time to CNS progression will involve comparing the rate of CNS progression in patients who receive pCSI to patients who receive IFRT. The cumulative incidence function (CIF) estimator will be used to estimate the median time to CNS progression in the presence of competing event of deaths in the two arms, separately. The Gray's test will be used to evaluate the difference in the distribution of CNS progression between treatment arms. These results will be interpreted in light of the competing deaths. The comparison of treatment effect on time to CNS progression will involve estimating the cause-specific hazard ratio (CHR) in a Cox proportional hazards model adjusting for patients and disease characteristics (e.g. stratification randomization factors).
Randomization until CNS progression, assessed up to 3 years
Time to radiation-induced CNS necrosis (TTRN)
Time Frame: Randomization until radiation necrosis in brain and/or spinal cord, assessed up to 3 years
Analysis will involve comparing the rate of radiation necrosis in patients who receive pCSI to patients who receive IFRT. Death will be treated as a competing risk event in this analysis. The cumulative incidence function (CIF) estimator will be used to estimate the median time to radiation-induced CNS necrosis in the presence of competing event of deaths in the two arms, separately. The Gray's test will be used to evaluate the difference in the distribution of TTRN between treatment arms. These results will be interpreted in light of the competing deaths. The comparison of treatment effect on TTRN will involve estimating the CHR in a Cox proportional hazards model adjusting for patients and disease characteristics (e.g. stratification randomization factors).
Randomization until radiation necrosis in brain and/or spinal cord, assessed up to 3 years
Incidence of treatment-related adverse events (AEs)
Time Frame: Baseline to 30 days from end of radiation therapy
Will be evaluated by comparative frequency summaries for all adverse event types between arms. AEs will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arms. Similarly, frequencies for specific potentially treatment related AEs where grade 3 or higher events are noted may be compared. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.
Baseline to 30 days from end of radiation therapy
Patient reported outcomes (PRO)
Time Frame: Baseline to 24 months post-radiation therapy
Will be assessed using MD Anderson Symptom Inventory for Brain Tumors and MD Anderson Symptom Inventory for Spine Tumors. Data from these four subscales will be analyzed separately. For each subscale, scores from individual questions will be averaged to arrive at a subscale-specific score for each patient. The symptom severity scores, symptom interference scores, and brain tumor-specific and spine tumor-specific scores will be summarized at each assessment timepoint using descriptive statistics and visualized with box plots and series plots. Changes over time will also be assessed visually. The comparison of changes in quality of life between treatment arms will be conducted separately for each of these four subscales using mixed effects models.
Baseline to 24 months post-radiation therapy

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimates of the primary outcome treatment effect by sex
Time Frame: Up to 3 years
Will estimate the primary outcome treatment effect and the corresponding 95% confidence intervals (CIs) by sex.
Up to 3 years
Estimates of the primary outcome treatment effect by race
Time Frame: Up to 3 years
Will estimate the primary outcome treatment effect and the corresponding 95% CIs by race.
Up to 3 years
Estimates of the primary outcome treatment effect by ethnicity
Time Frame: Up to 3 years
Will estimate the primary outcome treatment effect and the corresponding 95% CIs by ethnicity.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jonathan T Yang, NRG Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2025

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

July 31, 2028

Study Registration Dates

First Submitted

July 8, 2024

First Submitted That Met QC Criteria

July 8, 2024

First Posted (Actual)

July 15, 2024

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 5, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-BN014 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2024-04895 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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